Women With Diabetes Face Greater Cancer Risk Than Men

Liam Davenport

July 20, 2018

Diabetes increases the risk of developing cancer more in women than it does in men, with women at greater risk of developing four cancers in particular, the results of a large-scale systematic review suggest.

The review, which involved data on more than 19 million individuals from 47 studies, revealed that women with diabetes have a 27% increased risk of all cancers than women without the condition, compared with a 19% increased risk for men with diabetes.

The team calculated women with diabetes had a 6% increased risk of all-site cancers in comparison with men with diabetes.

The research, which was published online by Diabetologia on 19th July, also showed that, versus men, women with diabetes had, specifically, an increased risk of developing kidney, oral and stomach cancer, and leukaemia, and a lower risk of developing liver cancer.

'No Clear Pattern'

Study author Sanne Peters, PhD, The George Institute for Global Health, University of Oxford, told Medscape Medical News that she and her colleagues were surprised that there "is no clear pattern" between the specific cancers that were associated with diabetes.

"It’s not like it’s all related to gastrointestinal cancers or to cancers in the blood or whatever, so it’s something we definitely need to dive into further."

The author suggests that the increased cancer risk in women with diabetes may be related to women typically being more likely than men to be undertreated, to receive less intensive care or to have lower adherence to medication.

In addition, women have been shown to have a longer average duration of impaired glucose tolerance than men and have more exposure to untreated hyperinsulinaemia.

Peters said that, if such mechanisms are borne out in further studies, "it may be that we need to reconsider our clinical guidelines for the diagnosis of diabetes, and maybe subsequently also to treat it more intensively in women than in men".

She pointed out, however, that "we don’t know whether that actually works because the treatments for diabetes, to control glucose levels for example, are generally equally as effective in women as in men".

Peters also noted that women who develop gestational diabetes "are seven times more likely to develop diabetes later in life compared to women who’ve never had a pregnancy with diabetes".

"So that’s, of course, a group of women that may benefit from more intense screening."

Diabetes and Cancer Cases Rising

The incidence of cancer has increased rapidly, as has the prevalence of diabetes. While diabetes has been linked to both all-site and some specific cancers, the available evidence has not as yet been systematically reviewed.

The researchers therefore searched the PubMed database for cohort studies published up to December 2016 that reported sex-specific relative risk (RR) estimates for the association between diabetes and cancer, adjusted for age.

To examine the association between diabetes and all-site cancer, the team identified 47 studies, involving 121 cohorts, 19,239,302 individuals and 1,082,592 events.

The RR for combined all-site cancer associated with diabetes was 1.27 for women (p<0.001) and 1.19 (p<0.001) for men, at a pooled women-to-men ratio of RRs (RRR) of 1.06 (p<0.001).

When the team looked at type 1 and type 2 diabetes separately, they found that the RRR was identical, at 1.06 (p<0.005 for type 1 diabetes and p<0.001 for type 2 diabetes).

The pooled RRR was not substantially altered by adjusting for study region, year of baseline study, ascertainment of diabetes, level of adjustment, quality of study, or absolute risk difference between men and women.

Looking at cancer incidence, whether or not fatal, revealed that the pooled women-to-men RRR was 1.10 (p<0.001), while that for cancer mortality was 1.03 (p=0.16).

Next, the team looked at 50 specific cancer sites for incidence, finding that the pooled maximum available adjusted RRR was significantly higher for women than men for four cancers.

These were kidney cancer (RRR=1.11, p<0.001), oral cancer (RRR=1.13, p=0.009), stomach cancer (RRR=1.14, p<0.001) and leukaemia (RRR=1.15, p=0.002).

In contrast, the pooled RRR was significantly lower for women than for men for liver cancer, at 0.88 (p=0.005).

The team concludes that "diabetes is a risk factor for all-site cancer in

both sexes, with a stronger effect in women than men".

They add: "Sex differences varied across the location of the cancer, heightening the importance of a sex-specific approach to quantification of the role of diabetes in cancer research, prevention and treatment."

This study received no external funding. Toshiaki Ohkuma is supported by the John Chalmers Clinical Research Fellowship of the George Institute. Peters is supported by a UK Medical Research Council Skills Development Fellowship. Mark Woodward is a National Health and Medical Research Council of Australia Principal Research Fellow.

Woodward is a consultant to Amgen. Both other authors declare that there is no duality of interest associated with their contribution to this manuscript.

Diabetologia 2018. doi: 10.1007/s00125-018-4664-5. Abstract.


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